Monocyte CD14 response following endotoxin exposure in cotton spinners and office workers.

BACKGROUND: Monocyte cell surface CD14 acts as the major lipopolysaccharide (LPS) binding structure, and as such is of interest in the etiology of LPS induced disease. METHODS: The objective was to assess change in monocyte cell surface CD14 and CD4+ CD25+ lymphocytes in a group of cotton workers exposed to LPS over a working week, and to compare this to changes in office workers. Twenty-five cotton workers and nine office workers were studied. Monocyte CD14 fluorescence was measured by flow cytometry, on samples taken pre-shift on a Monday morning (baseline/pre-exposure), and subsequently after 6 and 72 hr. The majority of cotton workers were exposed to at least 1 EU/m(3) of endotoxin over a working shift, and some highly exposed (between 100 and 400 EU/m(3)). RESULTS: After 6 hr of work in the mill, cotton workers developed a significant upregulation in CD14 in comparison to office workers (P = 0.016), whereas CD14 expression had returned to levels not significantly differing from the office workers at 72 hr after first work exposure (P = 0.426). CONCLUSIONS: We propose that CD14 expression on monocytes may help to determine the mechanism of action of lipopolysaccharide in producing respiratory ill health, and may ultimately play a role in monitoring the health effect associated with LPS exposure in the workplace.

Airborne microorganisms associated with grain handling.

There is substantial evidence that workers handling grain develop allergic respiratory symptoms. Microbiological contaminants are likely to be a significant contributing factor. Worker's exposure to microorganisms contaminating grain dust in the UK was therefore examined. Aerobiological studies were made when grain was being handled on farms and also during bulk handling of grain in dockside terminals. A quantitative and qualitative microbiological examination of the airborne grain dust was carried out. Samples of airborne grain dust were collected and viable bacteria, fungi and actinomycetes were grown, isolated and identified. It was found that workers handling grain or working close to grain at farms and docks were frequently exposed to more than 1 million bacteria and fungi per m3 air, and that airborne bacteria and fungi exceeded 10(4) per m3 air in all areas sampled. The qualitative examination of the samples showed that the predominant microorganisms present differed between freshly harvested grain and stored grain, but not between different types of grain.

Amino acid residues that influence Fc epsilon RI-mediated effector functions of human immunoglobulin E.

Immunoglobulin E (IgE) mediates its effector functions via the Fc region of the molecule. IgE binding to and subsequent aggregation of the high-affinity receptor (Fc epsilon RI) by allergen plays a pivotal role in type I hypersensitivity responses. Earlier studies implicated the C epsilon 2 and 3 interface and the A-B loop in C epsilon 3 in the IgE-Fc epsilon RI interaction. These regions and glycosylation sites in C epsilon 3 were now targeted by site-specific mutagenesis. IgE binding to Fc epsilon RI was compared with surface plasmon resonance (SPR) measurements, which assessed the binding of the soluble extracellular domain of Fc epsilon RI to IgE. Kinetic analysis based on a pseudo-first-order model agrees with previous determinations. A more refined SPR-based kinetic analysis suggests a biphasic interaction. A model-free empirical analysis, comparing the binding strength and kinetics of native and mutant forms of IgE, identified changes in the kinetics of IgE-Fc epsilon RI interaction. Conservative substitutions introduced into the A-B loop have a small effect on binding, suggesting that the overall conformation of the loop is important for the complementary interaction, but multiple sites across the C epsilon 3 domain may influence IgE-Fc epsilon RI interactions. Asn394 is essential for the generation of a functional IgE molecule in mammalian cells. A role of Pro333 in the maintenance of a constrained conformation at the interface between C epsilon 2-3 emerged by studying the functional consequences of replacing this residue by Ala and Gly. These substitutions cause a dramatic decrease in the ability of the ligand to mediate stimulus secretion coupling, although only small changes in the association and dissociation rates are observed. Understanding the molecular basis of this phenomenon may provide important information for the design of inhibitors of mast cell degranulation.